teicoplanin pseudoaglycone

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: teicoplanin pseudoaglycone
• 英文别名: Glucosamine teicoplanin；(1S,2R,19R,22R,34S,37R,40R,52S)-2-[(2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22-amino-64-[(2S,3R,4R,5S,6R)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-5,15-dichloro-26,31,44,49-tetrahydroxy-21,35,38,54,56,59-hexaoxo-47-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-7,13,28-trioxa-20,36,39,53,55,58-hexazaundecacyclo[38.14.2.23,6.214,17.219,34.18,12.123,27.129,33.141,45.010,37.046,51]hexahexaconta-3,5,8,10,12(64),14,16,23(61),24,26,29(60),30,32,41(57),42,44,46(51),47,49,62,65-henicosaene-52-carboxylic acid
• 化学式: C₇₈H₇₉Cl₂N₉O₃₂
• 分子量: 1725.43
• InChiKey: NROYOOGFEWKMMB-GGLMYLAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.8
• 重原子数：
  121
• 可旋转键数：
  11
• 环数：
  16.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  659
• 氢给体数：
  24
• 氢受体数：
  34

反应信息

• 作为反应物：
  描述：

  succinyl-CoA 、 teicoplanin pseudoaglycone 在 N-acyltransferase Orf₁₁ 作用下， 以 aq. buffer 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Multiple Complexes of Long Aliphatic N-Acyltransferases Lead to Synthesis of 2,6-Diacylated/2-Acyl-Substituted Glycopeptide Antibiotics, Effectively Killing Vancomycin-Resistant Enterococcus

  摘要：

  Teicoplanin A2-2 (Tei)/A40926 is the last-line antibiotic to treat multidrug-resistant Gram-positive bacterial infections, e.g., methicillinresistant Staphylococcus aurcus (MRSA) and vancomycin-resistant enterococcus (VRE). This class of antibiotics is powered by the N-acyltransferase (NAT) Orf11*/Dbv8 through N-acylation on glucosamine at the central residue of Tei/A40926 pseudoaglycone. The NAT enzyme possesses enormous value in untapped applications; its advanced development is hampered largely due to a lack of structural information. In this report, we present eight high-resolution X-ray crystallographic unary, binary, and ternary complexes in order to decipher the molecular basis for NAT's functionality. The enzyme undergoes a multistage conformational change upon binding of acyl-CoA, thus allowing the uploading of Tei pseudoaglycone to enable the acyl-transfer reaction to take place in the occlusion between the N- and C-halves of the protein. The acyl moiety of acyl-CoA can be bulky or lengthy, allowing a large extent of diversity in new derivatives that can be formed upon its transfer. Vancomycin/synthetic acyl-N-acetyl cysteamine was not expected to be able to serve as a surrogate for an acyl acceptor/donor, respectively. Most strikingly, NAT can catalyze formation of 2-N,6-O-diacylated or C6 -> C2 acyl-substituted Tei analogues through an unusual 1,4-migration mechanism under stoichiometric/solvational reaction control, wherein selected representatives showed excellent biological activities, effectively counteracting major types (VanABC) of VRE.

  DOI：

  10.1021/ja504125v

文献信息

• Multiple Complexes of Long Aliphatic <i>N</i>-Acyltransferases Lead to Synthesis of 2,6-Diacylated/2-Acyl-Substituted Glycopeptide Antibiotics, Effectively Killing Vancomycin-Resistant Enterococcus
  作者：Syue-Yi Lyu、Yu-Chen Liu、Chin-Yuan Chang、Chuen-Jiuan Huang、Ya-Huang Chiu、Chun-Man Huang、Ning-Shian Hsu、Kuan-Hung Lin、Chang-Jer Wu、Ming-Daw Tsai、Tsung-Lin Li

  DOI：10.1021/ja504125v

  日期：2014.8.6

  Teicoplanin A2-2 (Tei)/A40926 is the last-line antibiotic to treat multidrug-resistant Gram-positive bacterial infections, e.g., methicillinresistant Staphylococcus aurcus (MRSA) and vancomycin-resistant enterococcus (VRE). This class of antibiotics is powered by the N-acyltransferase (NAT) Orf11*/Dbv8 through N-acylation on glucosamine at the central residue of Tei/A40926 pseudoaglycone. The NAT enzyme possesses enormous value in untapped applications; its advanced development is hampered largely due to a lack of structural information. In this report, we present eight high-resolution X-ray crystallographic unary, binary, and ternary complexes in order to decipher the molecular basis for NAT's functionality. The enzyme undergoes a multistage conformational change upon binding of acyl-CoA, thus allowing the uploading of Tei pseudoaglycone to enable the acyl-transfer reaction to take place in the occlusion between the N- and C-halves of the protein. The acyl moiety of acyl-CoA can be bulky or lengthy, allowing a large extent of diversity in new derivatives that can be formed upon its transfer. Vancomycin/synthetic acyl-N-acetyl cysteamine was not expected to be able to serve as a surrogate for an acyl acceptor/donor, respectively. Most strikingly, NAT can catalyze formation of 2-N,6-O-diacylated or C6 -> C2 acyl-substituted Tei analogues through an unusual 1,4-migration mechanism under stoichiometric/solvational reaction control, wherein selected representatives showed excellent biological activities, effectively counteracting major types (VanABC) of VRE.